Abstract:
Purpose:This study is to investigate the corneal anomaly caused by excess transforming growth factor-α (TGF-α) during mouse development. Methods:Bitransgenic KeraRT/TGF-α mice, generated via cross-mating tetO-TGF-α and KeraRT mice, were induced to overexpress TGF-α by doxycycline commencing at embryonic day 0 or postnatal day 0 to different developmental stages. Bitransgenic mice with doxycycline induction were defined as TGF-αECK mice (TGF-α excess expression by corneal keratocytes). Mouse eyes were examined by hematoxylin and eosin staining, immunofluorescent staining and transmission electron microscopy. Protein and RNA from mouse cornea were subjected to western blotting and real-time quantitative polymerase chain reaction. Results:In TGF-αECK mice, TGF-α overexpression resulted in corneal opacity. Excess TGF-α initially caused corneal epithelial hyperplasia and subsequent epithelium degeneration as the mouse developed, which was accompanied by gradually diminished K12 expression from the periphery of corneal epithelium and increased K13 expression toward the corneal center. Interestingly, K14 was detected in all layers of corneal epithelium of TGF-αECK mice, whereas it was limited at basal layer of controls. Transmission electron microscopy showed desmosome loss between corneal epithelial cells of TGF-αECK mice. In TGF-αECK mice, keratocan expression was abolished; α-SMA expression was increased while expression of Col1a1, Col1a2, and Col5a1 was diminished. Cell proliferation increased in the corneal epithelium and stroma, but not in the endothelium of TGF-αECK mice. Conclusions:Excess TGF-α had detrimental effects on corneal morphogenesis during mouse development in that it changed the cell fate of corneal epithelial cells to assume conjunctival phenotypic expression of K13, and keratocytes to myofibroblast phenotype.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Zhang L,Yuan Y,Yeh LK,Dong F,Zhang J,Okada Y,Kao WWY,Liu CY,Zhang Ydoi
10.1167/iovs.61.8.20subject
Has Abstractpub_date
2020-07-01 00:00:00pages
20issue
8eissn
0146-0404issn
1552-5783pii
2770318journal_volume
61pub_type
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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journal_title:Investigative ophthalmology & visual science
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更新日期:2010-12-01 00:00:00
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更新日期:2009-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1167/iovs.04-0043
更新日期:2005-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1995-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
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doi:
更新日期:1991-08-01 00:00:00
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更新日期:2009-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1997-02-01 00:00:00
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更新日期:2006-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
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更新日期:2013-12-17 00:00:00